Abstract 2643
Background
The BARCODE2 trial is investigating the response to platinum chemotherapy in men with advanced prostate cancer (PrCa) and a germline mutation in a DNA repair gene. We present the germline DNA sequencing results for 94 men who underwent genetic screening.
Methods
Eligible men with advanced PrCa consented to trial entry and provided a blood sample for DNA extraction and sequencing. All patients were known to have metastatic castration resistant PrCa (mCRPC) and had been treated with one or both of: Docetaxel chemotherapy and an androgen receptor targeted agent. Next generation sequencing (NGS) using a customised 115 gene panel (Agilent Technologies) was carried out on a MiSeq machine. Protein truncating variants (PTVs) in DNA repair genes by NGS were validated by Sanger sequencing. Patients found to carry a PTV were eligible to receive carboplatin upon disease progression.
Results
94 patients have undergone genetic testing. The median age of patients entering the trial was 67 (range 46-84). 21 patients (22%) carried one or more PTVs in a DNA repair gene: 3 carriers of a BRCA2 variant and 3 carriers of a variant in ALKBH3, 2 carriers of an ATM variant and 2 carriers of a PALB2 variant. One of the ATM variant carries also carried a PTV in POLQ and 2 further carriers of the same POLQ variant were identified. One carrier was identified to carry a variant in each of the following genes: MRE11A, PARP2, BLM, CHEK2, EXO1, LIG4, FANCD2, MSH5 and PMS1. Of the 20 identified PTVs, 11 are classified as pathogenic or likely pathogenic in ClinVar. There was no significant difference in the age at PrCa diagnosis between carriers and non-carriers (mean age 59 years vs 60; p = 0.34). There was also no difference in the presence of a family history of cancer.
Conclusions
The initial NGS results in the BARCODE2 trial demonstrate a higher frequency of germline mutations in mCRPC patients compared with previously published data. This study is ongoing and aims to sequence 450 patients. If the frequency of germline mutations in men with advanced PrCa is confirmed to be 20% or higher, this would support the roll-out of routine genetic testing in the oncology setting to identify men who may benefit from targeted treatments such as platinum chemotherapy and PARP inhibitors.
Clinical trial identification
NCT02955082.
Editorial acknowledgement
Legal entity responsible for the study
Institute of Cancer Research.
Funding
European Research Council.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2600 - Atezolizumab (atezo) vs chemotherapy (chemo) in patients (pts) with platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): a long-term overall survival (OS) and safety update from the Phase III IMvigor211 study
Presenter: Michiel Van der Heijden
Session: Poster Display session 3
Resources:
Abstract
3598 - Three-Year Follow-Up From the Phase 3 KEYNOTE-045 Trial: Pembrolizumab (Pembro) Versus Investigator’s Choice (Paclitaxel, Docetaxel, or Vinflunine) in Recurrent, Advanced Urothelial Cancer (UC)
Presenter: Andrea Necchi
Session: Poster Display session 3
Resources:
Abstract
2382 - First Report of Efficacy and Safety From a Phase 2 Trial of Tislelizumab, an Anti-PD-1 Antibody, for the Treatment of PD-L1+ Locally Advanced or Metastatic Urothelial Carcinoma (UC) in Asian Patients
Presenter: Dingwei Ye
Session: Poster Display session 3
Resources:
Abstract
2388 - Quality of Life of Metastatic Urothelial Cancer (mUC) Patients Treated with Enfortumab Vedotin (EV) Following Platinum-Containing Chemotherapy and a Checkpoint Inhibitor (CPI): Data from EV-201 Cohort 1
Presenter: Bradley McGregor
Session: Poster Display session 3
Resources:
Abstract
3748 - Safety and efficacy of atezolizumab (atezo) in patients (pts) with autoimmune disease (AID): subgroup analysis of the SAUL study in locally advanced/metastatic urinary tract carcinoma
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
1126 - Validation of the VIO prognostic index in patients with metastatic urothelial carcinoma treated with immune-checkpoint inhibitors
Presenter: Rafael Morales Barrera
Session: Poster Display session 3
Resources:
Abstract
3693 - Pathologic outcomes after neoadjuvant chemotherapy for high-risk muscle invasive bladder cancer
Presenter: Justin Matulay
Session: Poster Display session 3
Resources:
Abstract
4840 - Analysis of response to prior therapies and therapies after treatment with erdafitinib in fibroblast growth factor receptor (FGFR)-positive patients (pts) with metastatic urothelial carcinoma (mUC)
Presenter: Arlene Siefker-Radtke
Session: Poster Display session 3
Resources:
Abstract
1221 - Clinical outcomes by sex with atezolizumab (atezo) monotherapy in patients (pts) with locally advanced/metastatic urothelial carcinoma (mUC)
Presenter: Jean Hoffman-censits
Session: Poster Display session 3
Resources:
Abstract
1715 - National Small Cell Bladder Cancer Audit: Results from 26 UK institutions
Presenter: Caroline Chau
Session: Poster Display session 3
Resources:
Abstract